Essential Roles of CD8⁺CD122⁺ Regulatory T Cells in the Maintenance of T Cell Homeostasis

Regulation of immune system is of paramount importance to prevent immune attacks against self-components. Mice deficient in the interleukin (IL)-2/IL-15 receptor β chain, CD122, are model animals of such immune attacks and characteristically have a high number of abnormally activated T cells. Here, we show that the transfer of CD8⁺CD122⁺ cells into CD122-deficient neonates totally prevented the development of abnormal T cells. Furthermore, recombination activating gene–2^−/− mice that received wild-type mice–derived CD8⁺CD122⁻ cells died within 10 wk after cell transfer, indicating that normal CD8⁺CD122⁻ cells become dangerously activated T cells in the absence of CD8⁺CD122⁺ T cells. CD8⁺CD122⁺ cells could control activated CD8⁺ or CD4⁺ T cells both in vivo and in vitro. Our results indicate that the CD8⁺CD122⁺ population includes naturally occurring CD8⁺ regulatory T cells that control potentially dangerous T cells.